Interconversion of mating types in homothallic strains of baker's yeast S. cerevisiae is an example of a metastable genetic switch in which alternation between two states of a single genetic locus is catalysed by the product of a separate locus. Recent work by ourselves and others has lead to the "cassette model" for mating type interconversion in which the switching event is proposed to occur through the transposition of intact genes. The switching process has features analogous to regulatory events in the development of multicellular organisms and to genetic rearrangements which have been implicated in the maturation of immunoglobulin genes in mammals. This proposal describes a combined genetic and biochemical approach toward determination of the mechanism of the mating type switch, including: (1) detailed genetic mapping of the structural genes at the mating type locus; (2) identification and cloning of the DNA from the mating type locus of strains in various genetic states; (3) heteroduplex analysis of the cloned sequences by electron microscopy to determine the nature of the switching event; (4) development of a bioassay for the factors which catalyse the switch, with the eventual goal of purifying the components of the reaction for in vitro study.